Background: and Purpose Whole-exome sequencing (WES) is a valuable tool for identifying causative mutations in adult moyamoya disease (MMD), thereby advancing our understanding of the genetic mechanisms underlying this condition. Here, we conducted the first WESbased association study aimed at identifying genetic modifiers implicated in MMD. Methods: This WES study involved 160 patients with MMD and 189 controls from a multicenter hospital-based biobank, and evaluated combined annotation-dependent depletion (CADD) scores. Mutant-allele frequencies were compared in 369,121 individuals derived from the UK Biobank (UKB) WES. Mutant-allele risk scores (MARSs) were created based on WESidentified mutations. Gene-based association analyses and pooled analyses in East-Asian populations were further performed. Results: Fourteen mutations reached the genome-wide significance criterion (p<5×10-8 ), among which the p.R4810K mutation in the ring finger protein 213 gene (RNF213) showed the strongest significance (odds ratio=117.4, p=8.54×10-24 ). Notably, two mutations—p.G576S (alpha-glucosidase [GAA]) and p.D54N (charged multivesicular body protein 6 [CHMP6])— exhibited high CADD scores of 32 and 25, respectively, whereas the RNF213 p.R4810K mutation demonstrated a moderate deleteriousness score of 10.63. Fourteen mutations exhibited significant differences in allele frequencies between patients and UKB controlled data (p<1×10-8 ).The MARS9 model (incorporating nine missense mutations) showed better predictability for MMD (90.89%). The analysis of gene-based associations revealed four candidate genes: GAA, RNF213, CHMP6, and CARD14 (p=5×10-19 to 4×10-7 ). The subsequent pooled analyses validated four mutations in East Asian populations: p.V1195M, p.D1331G, p.S2334N, and p.R4810K (p<3×10-8 ). Conclusions This pioneering study has corroborated the significance of p.R4810K and identified several causative mutations predisposing patients to MMD, which helps to improve the understanding of its polygenetic nature.

Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

The optimal frequency for hemodialysis in older adults with end-stage kidney disease (ESKD) has not been established. This study aims to investigate whether a twice-weekly dialysis schedule using an incremental approach can reduce hospitalization rates in the elderly with incident dialysis, compared with conventional thrice-weekly dialysis. Methods: We have designed a pragmatic randomized controlled trial to compare the effects of twice-weekly versus thrice-weekly hemodialysis in 428 ESKD individuals (dropout rate 20%) aged 60 years or older with residual kidney function (urine output, >500 mL/ day). The trial will be conducted across 18 referral hospital-based dialysis centers in Korea. Individual participants will be randomized to either a twice-weekly (with incremental approach) or thrice-weekly dialysis group and will be followed up for 24 months. The primary outcome of the study is all-cause hospitalization rate, while secondary outcomes include dialysis-specific hospitalization rates, mortality, quality of life, frailty, and cost-effectiveness. Participants have the flexibility to transfer to other dialysis centers as needed. The decision to increase dialysis frequency will be made by the treating physicians. The study is ongoing and will be completed in May 2026. Conclusion: This study will provide valuable insights into the benefits and risks of twice-weekly dialysis with an incremental approach in elderly with residual kidney function compared to thrice-weekly dialysis.

Background: With the aging population and advancements in medical care worldwide, the number of older patients with end-stage kidney disease continues to rise. This study aimed to identify factors associated with osteoporosis and osteopenia in older patients undergoing incident hemodialysis and assess their impact on mortality. Methods: We analyzed a large multicenter retrospective cohort of patients aged ≥70 years undergoing incident hemodialysis to identify factors associated with osteoporosis using logistic regression analysis and to assess the association of death with osteoporosis and osteopenia using Cox multivariable analysis. Results: Among 710 patients, 39.0% and 19.6% had osteoporosis and osteopenia, respectively. Osteoporosis was significantly associated with female sex, a history of fractures, and the absence of phosphate binder use. During a median follow-up of 36.8 months, 348 participants (58.8%) died. Mortality rates were the highest in the osteoporosis group (79.8%), followed by the osteopenia (77.2%) and normal bone mineral density (BMD) groups (35.2%). Cox regression analysis revealed that even after adjusting for covariates, the osteoporosis group was significantly associated with a higher mortality risk than the normal BMD group. Osteoporosis at the start of hemodialysis was significantly associated with higher mortality. Conclusion We should consider the importance of bone health in patients undergoing incident hemodialysis and pay attention to the use of phosphate binders and fracture prevention.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13–1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84–1.11), 1.10 (0.96–1.27), 1.24 (1.06–1.45), 1.37 (1.12–1.66), and 1.99 (1.42–2.79), respectively (p for trend < 0.001). Conclusion In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.

Secondary dyslipidemia, characterized by elevated blood cholesterol and triglycerides, arises from various underlying conditions. The identification and appropriate handling of these causes is crucial for effective treatment. Major contributors include unhealthy diets, diseases impacting lipid metabolism, and medication side effects. Prioritizing the correction of secondary causes before initiating conventional lipid-lowering therapies is essential. Subsequent lipid profiles guide the selection of appropriate guideline-based lipid-lowering interventions.

Background: Hearing level reference values based on the results of recent audiometry have not been established for the general population of South Korea. This study aimed to evaluate the mean hearing levels of each age group and to measure the annual progression of hearing loss. Methods: We used the database of the eighth and ninth Korea National Health and Nutrition Examination Survey from 2020 to 2022, and included participants with normal tympanic membranes and without occupational noise exposure. Mean hearing levels were calculated by averaging hearing levels at 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz. Hearing loss was defined as a hearing level exceeding 25 dB in the better ear, and severity of hearing loss was classified as moderate, moderately severe, severe, and profound, following the World Health Organization classification. Results: Hearing levels and the proportions of patients with hearing loss increased with age. Hearing levels were 9.11 ± 6.28 dB, 13.33 ± 7.85 dB, 19.90 ± 10.30 dB, and 31.95 ± 13.37 dB in those in their 40s, 50s, 60s, and 70s, respectively, and the proportions of patients with hearing loss were 1.81%, 7.51%, 25.32%, and 63.94%, respectively. The annual increase in hearing level was 0.71 dB, and increases were greater at higher frequencies. Hearing loss was also worse in men. Conclusion The present study provides reference values for normal hearing levels by age group, and indirectly reveals the progression of age-related hearing loss. Based on the results, physicians will be able to provide appropriate advice regarding hearing levels and the need for monitoring in the elderly.

Background: Hearing level reference values based on the results of recent audiometry have not been established for the general population of South Korea. This study aimed to evaluate the mean hearing levels of each age group and to measure the annual progression of hearing loss. Methods: We used the database of the eighth and ninth Korea National Health and Nutrition Examination Survey from 2020 to 2022, and included participants with normal tympanic membranes and without occupational noise exposure. Mean hearing levels were calculated by averaging hearing levels at 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz. Hearing loss was defined as a hearing level exceeding 25 dB in the better ear, and severity of hearing loss was classified as moderate, moderately severe, severe, and profound, following the World Health Organization classification. Results: Hearing levels and the proportions of patients with hearing loss increased with age. Hearing levels were 9.11 ± 6.28 dB, 13.33 ± 7.85 dB, 19.90 ± 10.30 dB, and 31.95 ± 13.37 dB in those in their 40s, 50s, 60s, and 70s, respectively, and the proportions of patients with hearing loss were 1.81%, 7.51%, 25.32%, and 63.94%, respectively. The annual increase in hearing level was 0.71 dB, and increases were greater at higher frequencies. Hearing loss was also worse in men. Conclusion The present study provides reference values for normal hearing levels by age group, and indirectly reveals the progression of age-related hearing loss. Based on the results, physicians will be able to provide appropriate advice regarding hearing levels and the need for monitoring in the elderly.